Long chain polyunsaturated fatty acids (PUFA's) [e.g., C18-C22 (Omega-3 and 6)] are generally found in plants and marine sources, and are widely accepted in commercial cosmetic and health applications due to their beneficial effects on metabolism. The most common essential fatty acids are linoleic acid (LA) [C18:2n6, Omega-6] and α-linolenic acid (α-LN) [C18:3n3, Omega-3], and are responsible for the production of prostaglandins (PG) that control blood vessels and other body functions. Eicosapentaenoic acid (EPA) [C20:5n3, Omega-3] and docosahexaenoic acid (DHA) [C22:6n3, Omega-3] may be formed through the conversion of dietary linolenic acid, and are known to be essential for health and nutrition, resulting in an increase in commercial interest in recent years. EPA and DHA, are known to be potent antiarryhthmic agents and also improve vascular endothelial function, help lower blood pressure, platelet sensitivity, and the serum triglyceride level. In 2005 Simpson et. al (The impact of long-chain n-3 polyunsaturated fatty acids on human health. Nutrition research reviews (2005), 18, pp. 113-29) concluded that there is strong evidence of the clinical benefit of this type of Omega-3 PUFA on cardiovascular diseases or rheumatoid arthritis. Palmitoleic acid (C16:1n7, Omega-7) has also recently begun to receive an increase in commercial interest and has shown beneficial effects on cholesterol, low-density lipoprotein cholesterol levels, and also on reducing muscle insulin resistance and preventing beta-cell apoptosis.
As shown in Tables 1 and 2, trans fatty acids, cholesterol, and saturated fats responsible for atherosclerosis are fairly common in vegetable oil, fish oil, and marine products. Additionally, Omega-3 PUFA's are beneficial in reducing cholesterol and the risk of myocardial infarction. Hypertriglyceridaemia, which causes an increase in serum triglyceride in blood level, can cause cardiovascular diseases that may be prevented by replacing saturated fats with Omega-3 PUFAs. Synthesis and subsequent purification of essential fatty acid ethyl esters provides an opportunity to separate unwanted saturated fat from essential fatty acids.
TABLE 1Fat content/EPA + DHA (g 100 g−1) ratio of somevarious fish, marine products, vegetables and oilsFat contentEPA + DHAFat content/(EPA + DHA)(g 100 g−1)(g 100 g−1)(g 100 g−1) ratioEel24.50.8329.51Hering17.82.726.54Sprat16.63.235.14Tuna15.53.374.60Salmon13.62.864.76Mackerel11.91.756.8Carp4.80.3016Sardine4.51.393.24Swordfish4.41.792.45Trout2.70.594.58Halibut1.70.513.33Cod0.60.183.33Haddock0.60.163.75Lobster1.90.209.5Shrimp1.40.304.66Mussels1.40.159.33Anchovy2.30.504.60Sardine13.92.445.70
TABLE 2Fat contentFat content/α-LN(g 100 g−1)α-LN (g 100 g−1)(g 100 g−1) ratioButter83.21.2069.3Lard100.00.98102.04Linseed oil100.054.21.84Soybean oil100.07.7012.98Rapeseed oil100.09.1510.93Walnut oil100.013.57.40Olive oil100.00.86625Vegetable oil80.02.4033.3Almonds54.10.26208.07Hazelnut61.60.15410.6Walnuts62.56.809.19Kale0.900.352.57Lettuce0.220.073.14Parsley0.360.123.00Potato0.110.025.5Cauliflower0.180.101.8Spinach0.300.132.31White cabbage0.200.092.22Wheat bran4.650.1629.06
While sources and applications of Omega-3s have been developed commercially, the use of purified fatty acids in nutrition applications may extend beyond Omega-3s. Purified Omega-6, 7 & 9's may also be used in nutrition, cosmetic, and nutraceutical application to provide a more complete health or personal care product. Yang et. al (Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes. Lipids in health and disease 10, 120 (2011)) showed that oral administration of palmitoleic acid (Omega-7) to KK-Ay mice dramatically improved their diabetic condition. Also, hyperglycemia and hypertriglyceridemia were reduced in the mice with the oral administration of palmitoleic acid, while palmitic acid (saturated fat) was completely ineffective in providing the same effects. Maedler et. al (Distinct Effects of Saturated and Monosaturated Fatty Acids on Beta-Cell Turnover and Function. Diabetes (January 2001), vol. 50, no. 1, pp. 69-76) showed the harmful effect of palmitate on β-cell turnover while in contrast, the monounsaturated palmitoleic acid does not affect β-cell apoptosis but instead promotes β-cell proliferation. In promoting β-cell proliferation, palmitoleic acid counteracted the negative effects of palmitate (an anion of palmitic acid) as well as improved β-cell function. Therefore purifying Omega-7 rich oil by removing saturated fat may provide Omega-7s in a beneficial form suited for nutrition applications. Such purified Omega-7 fractions may be produced by synthesis of ethyl esters and their purification.
In addition to purified Omega-7s, purified Omega-6s also have an important role in the commercial nutrition market. The ratio of essential fatty acids is crucial to nutrition, as western diets are generally deficient in Omega-3 fatty acids and have excessive amounts of Omega-6 fatty acids. According to Simopoulos et. al (Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomedicine & pharmacotherapy (2006), 60, pp. 502-507; The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & pharmacotherapy (2002), 56, pp. 365-379), a lower ratio of Omega-6/Omega-3 fatty acids is desirable for reducing the risk of many chronic diseases. Synthesis of ethyl esters and their subsequent purification provides the opportunity for formulation of nutritionally relevant ratios of essential fatty acids like Omega-3 and Omega-6. Therefore, there is a need in the art for methods of producing high purity esters of Omega 3, 6, 7, & 9 fatty acids for use in nutrition, cosmetic, and nutraceutical products.